A presentation on Paul Ehrlich developed modern chemotherapy. This was my ppt for the module pharmaceutics 6. It i based on Anti microbial chemo; hope it help others doing relating things.

1. PAUL EHRLICH DEVELOPED MODERN
CONCEPT OF CHEMOTHERAPY AND
CHEMOTHERAPEUTIC AGENTS
Presented by
Naraino Majie Nabiilah &
Joorawon Svenia
Date: 21st October2014

2. Table of Contents
• Introduction
• Biography of Paul Ehrlich
• Development of chemotherapy
• Antimicrobial chemotherapy
• General characteristics of antimicrobial drugs
• Determination of antimicrobial drug activity
• Chemotherapeutic agents and their mechanism of
action
• Factors influencing the effectiveness of
antimicrobial drugs
• Antimicrobial resistance
• Conclusion

3. INTRODUCTION

4. INTRODUCTION
• Chemotherapy is the treatment of disease
through customized chemical compounds
which have specific biological targets and do
not attack the entire organism which contains
the target.
• Dr. Paul Ehrlich was the first person to treat
disease using chemicals.
• Before him medical treatments were broad
spectrum.
• He fathered the idea that a medical treatment
could be custom made to target the specific
cause of disease.

5. INTRODUCTION
• Paul Ehrlich had been searching for
chemicals that could kill infectious microbes
without harming their human hosts.
• Chemotherapeutic agents (CA) are chemical
agents that are used to treat disease.
• Antibiotics are microbial products or their
derivatives that kill or inhibit susceptible
microorganisms

6. BIOGRAPHY

7. BIOGRAPHY
• Born March 14, 1854
• He was a microbe hunter
• Cartooned as Doctor Phantasus
• Known as the father of chemotherapy
• Ehrlich defined chemotherapy as the use of
chemical substances, especially those produced
synthetically, to destroy pathogenic
microorganisms within the body.
• He was a revolutionist-interested in Histological
stain

8. BIOGRAPHY
• He studies how WBC would stain.
• This led to the discovery of methyl violet
used to stain G+ bacteria and safranin for G-bacteria.
• In 1878, he had his own laboratory where he
developed method of staining tubercule
bacillus.
• He was infected with tuberculosis in 1887,
went to Egypt and recovered after treatment.

9. BIOGRAPHY
• Came back and attempted to find a cure for
diphtheria.
• In 1892, diphtheria antitoxin successfully
produced.
• Awarded Nobel prize for this discovery.
• Wanted to produce a magic substance which
will target the desired site only.
• Birth of Antimicrobial chemotherapy.
– Tryptan red aka arsenophenol glycine and
arsenic containing compounds were found
to be effective against trypanosomes.

10. BIOGRAPHY
• In 1907, Salvarsan was used against
trypanosomes but was uneffective.
• Salvarsan was found to be effective against
syphilis and this remained the most effective
drug until discovery of penicillin by Fleming.
• Chemotherapy research went on while
Ehrlich health was declining.
• Died in August 1915 at the age of 61.
• Now, the concept of Ehrlich chemotherapy is
being employed in modern chemotherapy.

11. DEVELOPMENT
OF
CHEMOTHERAPY

12. DEVELOPMENT OF CHEMOTHERAPY
• Paul Ehrlich (1904–1909)—aniline dyes and
arsenic compounds
• Gerhard Domagk, and Jacques and Therese
Trefouel (1939)—sulfanilamide
• Ernest Duchesne (1896) discovered penicillin,
however, this discovery was not followed up
• Alexander Fleming (1928) accidentally
discovered the antimicrobial activity of
penicillin on a contaminated plate; however,
follow-up studies did not show the drug would
remain active in the body long enough to be
effective

13. DEVELOPMENT OF CHEMOTHERAPY
• Howard Florey and Ernst Chain (1939) aided
by the biochemist, Norman Heatley, worked
from Fleming’s published observations,
obtained a culture from him, and
demonstrated the effectiveness of penicillin
• Selman Waksman (1944)—streptomycin; this
success led to a worldwide search for
additional antibiotics, and the field has
progressed rapidly since then

14. ANTIMICROBIAL
CHEMOTHERAPY

15. ANTIMICROBIAL CHEMOTHERAPY
• The foundation of the 20th century
chemotherapy was built on a search of
antiprotozoal agents to be used against malaria
and African sleeping sickness
(trypanosomiasis).
• The chemotherapeutic agents interfere directly
with the multiplication of organisms and in
concentrations not harmful to the host.

16. ANTIMICROBIAL CHEMOTHERAPY
• Paul Ehrlich formulated the principles of
selective toxicity and recognized the specific
chemical relationship between parasites and
drugs.
• He introduced arsphenamine, an organic
Selective toxicity is the
ability to kill or inhibit
microbial pathogen with
minimal side effects to the
host
compound of arsenic, as a cure for syphillis
and other spirochetal diseases.
• Likewise, the organic arsenicals, and
synthetic dyes, like trypan blue, were also
found useful in the treatment of
trypanosomiasis.

17. GENERAL
CHARACTERISTICS
OF
ANTIMICROBIAL
DRUGS

18. GENERAL CHARACTERISTICS OF
ANTIMICROBIAL DRUGS
• Selective toxicity—ability to kill or inhibit
microbial pathogen with minimal side effects
in the host
– Therapeutic dose—the drug level required
for clinical treatment of a particular
infection
– Toxic dose—the drug level at which the
agent becomes too toxic for the host
(produces undesirable side effects)
– Therapeutic index—the ratio of toxic dose to
therapeutic dose: the larger the better

19. GENERAL CHARACTERISTICS OF
ANTIMICROBIAL DRUGS
• Chemotherapeutic agents can occur naturally,
be synthetic, or semisynthetic (chemical
modifications of naturally occurring
antibiotics)
• Drugs with narrow-spectrum activity are
effective against a limited variety of
pathogens;
• Drugs with broad-spectrum activity are
effective against a wide variety of pathogens

20. GENERAL CHARACTERISTICS OF
ANTIMICROBIAL DRUGS
• Drug can be cidal (able to kill) or static (able to
reversibly inhibit growth)
• Minimal inhibitory concentration (MIC) is the
lowest concentration of the drug that prevents
growth of a pathogen;
• Minimal lethal concentration (MLC) is the
lowest drug concentration that kills the
pathogen

21. DETERMINING THE
LEVEL OF
ANTIMICROBIAL
ACTIVITY

22. DETERMINING THE LEVEL OF
ANTIMICROBIAL ACTIVITY
• Dilution susceptibility tests—
– a set of broth-containing tubes are prepared;
– each tube in the set has a specific antibiotic
concentration;
– to each is added a standard number of test
organisms
– The lowest concentration of the antibiotic
resulting in no microbial growth is the MIC
– Tubes showing no growth implies the lowest
concentration of the drug from which the
organism does not recover; this is the MLC

23. DETERMINING THE LEVEL OF
ANTIMICROBIAL ACTIVITY
• Disk diffusion tests
– Disks impregnated with specific drugs are
placed on agar plates inoculated with the
test organism;
– clear zones (no growth) will be observed
if the organism is sensitive to the drug;
– the size of the clear zone is used to
determine the relative sensitivity;
– zone width also is a function of initial
concentration, solubility, and diffusion
rate of the antibiotic

24. DETERMINING THE LEVEL OF
ANTIMICROBIAL ACTIVITY
• The Etest®
– Especially useful for testing anaerobic
microorganisms
– Makes use of special plastic strips that
contain a concentration gradient of an
antibiotic;
– Each strip is labeled with a scale of MIC
values;
– After incubation an elliptical zone of
inhibition is observed and its intersection
with the strip is used to determine the MIC

25. CHEMOTHERAPEUTIC
AGENTS AND THEIR
MECHANISM OF
ACTION

26. Antibacterial Drugs
1. Inhibitors of cell wall synthesis are effective
and selective because bacterial cell walls have
unique structures not found in eukaryotic cells
– Penicillin
– Cephalosporins
– Vancomycin and teicoplanine

27. Antibacterial Drugs
2. Protein synthesis inhibitors exploit the
differences between prokaryotic and eukaryotic
ribosomes
– Aminoglycosides
– Tetracyclines
– Macrolides
– Chloramphenicol

28. Antibacterial Drugs
3. Metabolic antagonists are structural analogs of
metabolic intermediates that act as
antimetabolites, inhibiting metabolic pathways;
bacteriostatic
– Sulfonamides or sulfa drugs
• inhibit folic acid synthesis in bacteria (humans
don’t synthesize folic acid, so are not affected);
• resistance is increasing and many patients are
allergic to these drugs;
• includes p-aminobenzoic acid (PABA)
– Trimethoprim
• synthetic antibiotic that blocks folic acid
production;
• broad spectrum often combined with sulfa drugs

29. Antibacterial Drugs
4. Nucleic acid synthesis inhibitors block
enzymes of transcription and translation;
generally not as selectively toxic
– Quinolones
• synthetic drugs that inhibit bacterial DNA
gyrase or topoisomerase II, thereby disrupting
replication, repair, and other processes
involving DNA;
• broad spectrum;
• includes nalidixic acid and ciprofloxacin
(Cipro)

30. Antifungal Drugs
• Fungal infections are more difficult to treat
than bacterial infections because
– the greater similarity of fungi and host
limits the ability of a drug to have a
selective point of attack;
– furthermore, many fungi have
detoxification systems that inactivate
drugs
• Superficial mycoses are infections of
superficial tissues and can often be treated by
topical application of antifungal drugs such
as miconazole, nystatin, and griseofulvin,
thereby minimizing systemic side effects

31. Antifungal Drugs
• Systemic mycoses are more difficult to treat
and can be fatal;
– amphotericin B and flucytosine have been
used with limited success because of its
toxicity;
• Subcutaneous mycoses (e.g., mycetomas) are
treated with a mixture of therapies

32. Antiviral Drugs
• Selectivity is a problem because viruses use the
metabolic machinery of the host
• Antiviral drugs target specific steps of life cycle,
including viral uncoating and DNA replication (e.g.,
amantadine, vidarabine, acyclovir, cidofovir, and
azidothymidine)
• Anti-HIV drugs (e.g., AZT, ddI, 3TC) have four
targets:
– nucleoside reverse transcriptase inhibitors (NRTIs),
– nonnucleoside reverse transcriptase inhibitors
(NNRTIs),
– protease inhibitors (block viral polypeptide
processing), and
– fusion inhibitors (block viral entry into cell);
combinations of drugs often used
• Tamiflu is a neuraminidase inhibitor that is used to
treat influenza

33. Antiprotozoan drugs
• Mechanisms of action for antiprotozoan drugs
are largely unknown; as protozoans and
humans are both eukaryotes, selective toxicity
is difficult to achieve

34. FACTORS
INFLUENCING THE
EFFECTIVENESS OF
ANTIMICROBIAL
DRUGS

35. FACTORS INFLUENCING THE EFFECTIVENESS
OF ANTIMICROBIAL DRUGS
• Drug’s ability to reach the site of infection—
this is greatly influenced by
– the mode of administration (e.g., oral,
topical, parenteral),
– by exclusion from the site of infections (e.g.,
blood clots or necrotic tissue protects
bacterium)
• Susceptibility of pathogen—influenced by
growth rate and by inherent properties (e.g.,
whether or not pathogen has target of the drug)

36. FACTORS INFLUENCING THE EFFECTIVENESS
OF ANTIMICROBIAL DRUGS
• Factors influencing drug concentration in the
body
– must exceed the pathogen’s MIC for the
drug to be effective;
– this will depend on the amount of drug
administered, the route of administration,
the speed of uptake, and the rate of
clearance (elimination) from the body
• Drug resistance has become an increasing
problem

37. DRUG RESISTANCE

38. DRUG RESISTANCE
• Bacteria have evolved many strategies for resisting
the action of antibiotics and antibacterial agents.
• Bacteria that produce antibiotics do so to gain a
selective advantage over other competing microbes
in their natural environment.
• If they were sensitive to their own metabolic
products, such a selective advantage would be lost.
• The problem of antibiotic resistance is becoming
increasingly as more and more strains of
pathogenic microorganisms are untreatable with
commonly used antimicrobial agents.

39. DRUG RESISTANCE
• Mechanisms of drug resistance
– Prevent entrance of drug (e.g., alter drug
transport into cell)
– Pump the drug out of the cell once it has
entered (efflux pump)
– Enzymatic inactivation of the drug
– Alteration of target enzyme or organelle
– Use of alternative pathways and increased
production of the target metabolite.

40. DRUG RESISTANCE
• Overcoming drug resistance
– Several strategies can be used to
discourage emergence of drug resistance
• administration of high doses,
• simultaneous treatment with more than one
drug,
• limited use of broad-spectrum antibiotics
– Development of new drugs and
exploration of new treatment methods
(e.g., phage treatment of bacterial
infections).

42. CONCLUSION
• From the basic research of Dr Ehrlich,
modern chemotherapy was developed.
• Many drugs are now being produced to
counteract the pathogens of many diseases.
• Modern chemotherapy is also being
employed in cancer treatment using the
concept of selective toxicity.
• Chemotherapeutic agents against infection
should be used appropriately to prevent
resistance.

43. REFERENCES
• Antimicrobial Chemotherapy By Roger Finch, Peter Davey, Mark H.
Wilcox, William Irving
• Chapter 11. ANTIBIOTICS AND CHEMOTHERAPEUTIC
AGENTS BY I.H.Siddique
http://compepid.tuskegee.edu/syllabi/pathobiology/microbiology/mic
ro201/chapter11.html
• Anon. General Characteristics of Antimicrobial.
http://dev6.mhhe.com/textflowdev/genhtml/0073375268/P8.34.2.htm
• Anon. Antimicrobial drugs.
http://classes.midlandstech.edu/carterp/Courses/bio225/chap20/lectur
e1.htm
• Talaro KP and Chess B. Foundations in Microbiology. Principle of
Antimicrobial Therapy. https://www.inkling.com/read/foundations-in-microbiology-
talaro-chess-8th/chapter-12/principles-of-antimicrobial
• Todar K. Antibiotics.
http://lecturer.ukdw.ac.id/dhira/ControlGrowth/antibiotic.html

44. THANK YOU